Rats treated with puromycin aminonucleoside (PAN) developed characteristics of the nephrotic syndrome, including albuminuria, hypoalbuminemia and hyperiipidemia. To study the regulation of apolipoprotein (apo) A-1 and apo E gene expression in nephrotic rats, we analyzed the steady-state levels (SSLs) of hepatic and intestinal apo A-1 and apo E mRNA using the Northern technique, and the plasma levels of high-density lipoprotein (HDL) by biochemical methods. Male Wistar rats were treated with PAN and compared with pair-fed and untreated control rats at different stages of disease. Nephrotic rats presented with marked hypoalbuminemia and albuminuria at between 6 and 11 days after PAN treatment. During this stage of disease, plasma levels of HDL were elevated in correlation with an increase of both hepatic and intestinal apo A-1 mRNA. In liver of nephrotic rats, high levels of apo A-1 mRNA together with low levels of apo E mRNA caused an increase in the ratio of apo A-1/apo E mRNA, reaching a maximum 6 days after treatment. Apo E mRNA was barely detected in small intestine of pair-fed controls and PAN-treated rats. However, contrary to nephrotic rats, the ratio apo A-1/apo E mRNA was inverted in liver of pair-fed rats due to an increase in apo E mRNA. In conclusion, in nephrotic rats, the SSL of apo A-1 mRNA is increased in liver and small intestine and appears to regulate the plasma levels of apo A-1. These results also suggest a coordinated regulation of the apo A-1 and apo E gene expression in liver of nephrotic and pair-fed rats.